The Pulse of Life: YSPH Study Reveals How Gene Expression Evolves

Researchers at the Yale School of Public Health have discovered the evolutionary rhythm of gene expression, showing that changes happen at strikingly varied rates.

In the study, published in Molecular Biology and Evolution, “we found that some genes’ expression patterns remain virtually frozen in place for hundreds of millions of years, while others adapt quickly, evolving their expression rapidly,” said Dr. Jeffrey Townsend, PhD, the study’s senior author, Elihu Professor of Biostatistics and Professor of Ecology and Evolutionary Biology at YSPH. “Knowing these rates of evolution shows us which genetic functions are the unchanging heartbeat of life—and which are evolution’s improvisations.”

Gene expression—the process by which DNA is transcribed into RNA and then translated into proteins—is central to how organisms develop and respond to their environments. Evolutionary shifts in DNA sequence have been documented, but changes in gene expression have been harder to quantify over long periods of time.

To tackle this challenge, Townsend led a team of investigators that examined over 3,900 genes in nine fungal species with comparable biological developmental stages. The team used diverse fungi for their analysis because they are easy to grow in a common environment. Because the species were meticulously cultured under identical conditions, it allowed the scientists to measure only genetic, not environmental, differences.

Lead author Yen-Wen Wang, PhD, a postdoctoral researcher in Townsend’s lab, applied sophisticated statistical models to infer how frequently gene expression doubled or halved across millions of years of evolution. For most genes, the time ranged from 400 to 900 million years. But some genes—particularly those involved in early spore germination—evolved much faster, in just 6.9 million years.

“This early germination stage is ecologically crucial,” explained Wang. “Fungi must adapt rapidly to capitalize on distinct ways to colonize environments and rapidly acquire nutrients. Their early germination genes are under strong pressure to change.”

By analyzing gene function across biological pathways, the researchers found that evolution tends to act more quickly on genes involved in flexible, responsive tasks—such as carbon metabolism—than enduring processes such as meiosis, a key aspect of sexual reproduction.

“These findings reveal how the role a gene plays in development affects the pace at which its expression evolves,” Townsend said. “If a gene is part of an ancient, important, tightly regulated process like meiosis, it can’t accommodate change. But if it’s in a metabolic pathway that responds to environmental shifts, there’s more room for evolutionary experimentation.”

The study establishes a powerful new framework for investigating gene evolution.

“Knowing which genes evolve quickly or slowly in their expression enables us to precisely target genes that are optimal targets for functional characterization and applications in nearly all fields of life sciences,” Townsend said, adding that it could be useful in biotechnology applications ranging from agriculture to medicine.

The work was funded by the U.S. National Science Foundation and National Institutes of Health. The data and methodological approach are publicly available. The researchers hope others will be inspired to expand our knowledge of gene expression in other key areas.

“Ultimately,” Townsend said, “we want to understand how the choreography of gene expression — its timing, location, and intensity — has evolved to build the immense diversity of life we see today.”

Transcriptome data from the study are publicly available in the Gene Expression Omnibus under PRJNA1171587 and PRJNA1177519.